GUANIDINOBENZOIC ACID INHIBITORS OF INFLUENZA-VIRUS NEURAMINIDASE

The active site of influenza virus neuraminidase (NA) is formed by 11 universally conserved residues. A guanidino group incorporated into tw o unrelated NA inhibitors was previously reported to occupy different negatively charged sites in the NA active site. A new inhibitor contai ning two guanidino groups was synthesized in order to utilize both sit es in an attempt to acquire a combined increase in affinity. The X-ray crystal structures of the complexes show that the expected increase i n affinity could not be achieved even though the added guanidino group binds to the negatively charged site as designed. This suggests that the ligand affinity to the target protein is contributed both from lig and-protein interactions and solvation/conformation energy of the liga nd. (C) 1997 Academic Press Limited.